Concentration-response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy.

Dolutegravir is associated with more weight gain than efavirenz in people starting antiretroviral therapy (ART). We investigated the concentration-response relationships of efavirenz and dolutegravir with weight gain. We determined concentration-response relationships of dolutegravir and efavirenz (both combined with tenofovir disoproxil fumarate and emtricitabine) with changes in weight and fat distribution, derived from dual-energy x-ray absorptiometry scans, in a nested study of ART-naïve participants from a randomised controlled trial. Pharmacokinetic parameters used in analyses were efavirenz mid-dosing interval concentrations and estimated dolutegravir area under the concentration-time curve using a population pharmacokinetic model developed in the study population. Study outcomes were percentage changes from baseline to week 48 in weight, and visceral and subcutaneous adipose tissue mass. Pharmacokinetic data were available for 158 and 233 participants in the efavirenz arm and dolutegravir arms respectively; 57.0% were women. On multivariable linear regression there were independent negative associations between efavirenz concentrations and changes in both weight (P < .001) and subcutaneous adipose tissue mass (P = .002). Estimated dolutegravir area under the concentration-time curve up to 24 hours was not associated with change in weight (P = .109) but was negatively associated with change in visceral adipose tissue mass (P = .025). We found an independent negative concentration-response relationship between efavirenz concentrations and weight change in ART-naïve participants. Dolutegravir concentrations were not independently associated with weight change. These findings suggest that weight gain differences between efavirenz and dolutegravir are driven by efavirenz toxicity impairing weight gain rather than by off-target effects of dolutegravir causing weight gain.

Relationship between sleep disorders, HIV status and cardiovascular risk: cross-sectional study of long-haul truck drivers from Southern Africa.

OBJECTIVES: Long-haul truck drivers (TDs) may have lifestyles that promote cardiovascular disease (CVD), including diet, sleep and activity issues. Most studies conducted among truckers investigated the relationship between poor sleep and cardiometabolic health, but none assessed whether suspected obstructive sleep apnoea (OSA) and shortened sleep were associated with markers of cardiometabolic risk. We determined whether sleep disorders and circadian misalignment were associated with chronic inflammation and CVD risk in TDs from Southern Africa. METHODS: Participants were recruited at roadside wellness centres in Gauteng and Free State Provinces, South Africa. OSA risk was assessed using the Berlin Questionnaire, while sleep duration and sleep quality were assessed using items from the Pittsburgh Sleep Quality Index. Clinical information, neck circumference (NC), metabolic profile, elevated BP, HIV status and C-reactive protein (CRP) were collected. CVD risk was assessed using the Framingham Risk Score (FRS). RESULTS: Out of 575 participants aged on average 37.7 years, 17.2% were at OSA risk, 72.0% had elevated BP, 9.4% had HIV and 28.0% were obese. Mean sleep duration was 7.4±1.8 hours, and 49.6% reported working night shift at least once a week. Shortened sleep, OSA risk, age, body mass index, NC and years as full-time TD were associated with greater FRS independently of HIV status and night shift. Working night shift was associated with higher CRP levels in HIV+ compared with HIV- participants. CONCLUSIONS: Circadian misalignment in HIV, and OSA and short sleep duration in all truckers were associated with increased CVD risk. Truckers should be given careful attention in terms of health management and sleep education.

Effects of Tobacco Usage and Antiretroviral Therapy on Biomarkers of Systemic Immune Activation in HIV-Infected Participants.

Like HIV infection, smoking, which is common among HIV-infected persons, is associated with chronic, systemic inflammation. However, the possible augmentative effects of HIV infection and smoking and other types of tobacco usage on indices of systemic inflammation and the impact of combination antiretroviral therapy (cART) thereon remain largely unexplored and represent the focus of the current study. Of the total number of HIV-infected persons recruited to the study (n = 199), 100 were categorised as pre-cART and 99 as virally suppressed (HIV viral load < 40 copies/mL). According to serum cotinine levels, 144 and 55 participants were categorised as nonusers and users of tobacco, respectively. In addition to cytokines (IL-6, IL-8, and TNF-α) and chemokines (IP-10, MIG, IL-8, MCP-1, and RANTES), other biomarkers of systemic inflammation included C-reactive protein (CRP), ß2-microglobulin, and those of neutrophil activation [ICAM-1, L-selectin, matrix metalloproteinase-9 (MMP-9)], microbial translocation (soluble CD14, LPS-binding protein), and oxidative stress (cyclophilin A, surfactant D). These were measured using multiplex bead array, ELISA, and immunonephelometric procedures. Viral suppression was associated with significant decreases in the levels of most of the biomarkers tested (P < 0.0037-0.0008), with the exceptions of CRP, cyclophilin A, and MMP-9. With respect to tobacco usage, irrespective of cART status, circulating levels of ß2-microglobulin, cyclophilin A, and RANTES were significantly elevated (P < 0.042-0.012) in users vs nonusers. Additional analysis of the groups of tobacco users and nonusers according to cART status revealed high levels of RANTES in pre-cART/tobacco users relative to the three other subgroups (P < 0.004-0.0001), while more modest increases in cyclophilin A and MMP-9 (P < 0.019-0.027) were observed in comparison with the cART/tobacco user subgroup. Notwithstanding the efficacy of cART in attenuating HIV-associated, chronic systemic inflammation, the current study has identified RANTES as being significantly and seemingly selectively increased in those with active HIV infection who use tobacco, a mechanism which may underpin augmentative proinflammatory activity.

HIV pre-exposure prophylaxis and early antiretroviral treatment among female sex workers in South Africa: Results from a prospective observational demonstration project.

BACKGROUND: Operational research is required to design delivery of pre-exposure prophylaxis (PrEP) and early antiretroviral treatment (ART). This paper presents the primary analysis of programmatic data, as well as demographic, behavioural, and clinical data, from the TAPS Demonstration Project, which offered both interventions to female sex workers (FSWs) at 2 urban clinic sites in South Africa. METHODS AND FINDINGS: The TAPS study was conducted between 30 March 2015 and 30 June 2017, with the enrolment period ending on 31 July 2016. TAPS was a prospective observational cohort study with 2 groups receiving interventions delivered in existing service settings: (1) PrEP as part of combination prevention for HIV-negative FSWs and (2) early ART for HIV-positive FSWs. The main outcome was programme retention at 12 months of follow-up. Of the 947 FSWs initially seen in clinic, 692 were HIV tested. HIV prevalence was 49%. Among those returning to clinic after HIV testing and clinical screening, 93% of the women who were HIV-negative were confirmed as clinically eligible for PrEP (n = 224/241), and 41% (n = 110/270) of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment. Of the remaining women who were HIV-positive, 93% were eligible for early ART (n = 148/160). From those eligible, 98% (n = 219/224) and 94% (n = 139/148) took up PrEP and early ART, respectively. At baseline, a substantial fraction of women had a steady partner, worked in brothels, and were born in Zimbabwe. Of those enrolled, 22% on PrEP (n = 49/219) and 60% on early ART (n = 83/139) were seen at 12 months; we observed high rates of loss to follow-up: 71% (n = 156/219) and 30% (n = 42/139) in the PrEP and early ART groups, respectively. Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days, with high levels of consistent condom use with clients and low use with steady partners in both study groups. There were no seroconversions on PrEP and 7 virological failures on early ART among women remaining in the study. Reported adherence to PrEP varied over time between 70% and 85%, whereas over 90% of participants reported taking pills daily while on early ART. Data on provider-side costs were also collected and analysed. The total cost of service delivery was approximately US$126 for PrEP and US$406 for early ART per person-year. The main limitations of this study include the lack of a control group, which was not included due to ethical considerations; clinical study requirements imposed when PrEP was not approved through the regulatory system, which could have affected uptake; and the timing of the implementation of a national sex worker HIV programme, which could have also affected uptake and retention. CONCLUSIONS: PrEP and early ART services can be implemented within FSW routine services in high prevalence, urban settings. We observed good uptake for both PrEP and early ART; however, retention rates for PrEP were low. Retention rates for early ART were similar to retention rates for the current standard of care. While the cost of the interventions was higher than previously published, there is potential for cost reduction at scale. The TAPS Demonstration Project results provided the basis for the first government PrEP and early ART guidelines and the rollout of the national sex worker HIV programme in South Africa.

Uptake of health services among truck drivers in South Africa: analysis of routine data from nine roadside wellness centres.

BACKGROUND: Long-distance truck drivers are occupationally susceptible to poor health outcomes. Their patterns of healthcare utilisation and the suitability of healthcare services available to them are not well documented. We report on truck driver healthcare utilisation across South Africa and characterise the client population of the clinics serving them for future service development. METHODS: We analysed anonymised data routinely collected over a two-year period at nine Roadside Wellness Centres. Associations between services accessed and socio-demographic characteristics were assessed using univariable and multivariable logistic regression models. RESULTS: We recorded 16,688 visits by 13,252 individual truck drivers (average of 1.26 visits/person) who accessed 17,885 services for an average of 1.07 services/visit and 1.35 services/person. The mean age of truck drivers was 39 years. Sixty-seven percent reported being in stable relationships. The most accessed services were primary healthcare (PHC)(62%) followed by HIV (32%). Low proportions (≤6%) accessed STI,TB and malaria services. Most visits were characterised by only one service being accessed (93%, n = 15,523/16,688). Of the remaining 7% of visits, up to five services were accessed per visit and the combination of TB /HIV services in one visit remained extremely low (<1%, n = 14/16,688). Besides PHC services at the beginning of the reporting period, all service categories displayed similar seasonal utilisation trends(i.e. service utilisation peaked in the immediate few months post clinics opening and substantially decreased before holidays). Across all service categories, younger truck drivers, those with a stable partner currently, and those of South African origin were the main clinic attendees. Older truck drivers (≥40 years) were more likely to access TB and PHC services, yet less likely to access HIV and STI services. Those with stable partners were less likely to access STI and TB services but more likely to access malaria and PHC services. South African attendees were more likely to access PHC, while attendees from other nationalities were more likely to access HIV and malaria services. CONCLUSIONS: This utilisation analysis shows that tailored services assist in alleviating healthcare access challenges faced by truck drivers, but it underscores the importance of ensuring that service packages and clinics speak to truck drivers' needs in terms of services offered and clinic location.

A Political and Social History of HIV in South Africa.

For the past 25 years, South Africa has had to deal with the inexorable and monumental rise of HIV. From one or two isolated cases, in the late 1980s, South Africa now has an estimated 6.4 million people infected with HIV, with high rates of concomitant tuberculosis, which will profoundly affect the country for decades to come. For nearly 10 years, the South African government's response to the HIV epidemic was described as denialist, which was estimated to have resulted in the deaths of 330,000 people because lifesaving antiretroviral therapy (ART) was not provided (Chigwedere et al. J Acquir Immune Defic Syndr. 49:410-15, 2008; Heywood 2004). However, the story of the HIV and AIDS response in South Africa over the past 5 years is one of great progress after almost a decade of complex and tragic denialism that united civil society in a way not seen since the opposition to apartheid. Today, South Africa can boast of close to 3 million people on ART, by far the largest number in the world. Prevention efforts appear to be yielding results but there continues to be large numbers of new infections, with a profound peak in incidence in young women aged 15 to 24 years. In addition, infections occur across the gender spectrum in older age groups. As a result of the massive increase in access to ART after 2004 and particularly after 2008 as political will towards the HIV ART programme improved, there has been a marked increase in life expectancy, from 56 to 61 years in the period 2009-2012 alone; the aggressive expansion of the prevention of mother to child transmission (PMTCT) to HIV-positive pregnant women has been accompanied by dramatic decrease in HIV transmission to infants; and a 25 % decrease in child and infant mortality rates in the period 2009-2012. This progress in access is significantly due to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

National Impact of SARS-CoV-2 Infection on HIV Virological Suppression in South Africa.

BACKGROUND: Coronavirus disease (COVID-19) severely disrupted routine health care globally. This study assessed the impact of successive COVID-19 waves on HIV viral load (VL) suppression in South Africa, using the national public sector laboratory database. Guidelines recommend VL monitoring at 6 months after treatment initiation, annually once if suppressed, or more frequently if unsuppressed. METHODS: Specimen-level VL data were extracted for the period January 2019-December 2021. We assessed the national percentage of samples with a VL <50 (virological suppression), 50-999 (low-level viremia), and ≥1000 (viremia) copies/mL. Data were analyzed by calendar year and month. Data for 2019 (pre-COVID-19) were compared with the 2020 and 2021 calendar years (lockdowns imposed). The national number of COVID-19 cases was reported to indicate the wave periods as follows: 1 (ancestral)-June-August 2020; 2 (Beta)-December 2020-January 2021; 3 (Delta)-June-August 2021, and 4 (Omicron)-December 2021. RESULTS: Data are reported for 17,460,264 samples, with 5,608,733, 5,840,056, and 6,011,475 tests performed in 2019, 2020, and 2021 respectively. Overall, a VL of <50, 50-999, and ≥1000 copies/mL were reported for 69.4%, 17.3%, and 13.4% of samples, respectively. A VL <50 copies/mL was reported for 67.7%, 70.3%, and 70.0% of patients in 2019, 2020, and 2021, respectively. For the 2020 and 2021 calendar years, the monthly percentage of patients with a VL <50 copies/mL ranged between 64.6% and 72.7%. CONCLUSION: Our findings indicate that COVID-19 has not had a substantial impact on the percentage of samples with virological suppression at the national level.

HIV Viral Load Testing in the South African Public Health Setting in the Context of Evolving ART Guidelines and Advances in Technology, 2013-2022.

HIV viral load (VL) testing plays a key role in the clinical management of HIV as a marker of adherence and antiretroviral efficacy. To date, national and international antiretroviral treatment recommendations have evolved to endorse routine VL testing. South Africa (SA) has recommended routine VL testing since 2004. Progressively, the centralised HIV VL program managed by its National Health Laboratory Service (NHLS) has undergone expansive growth. Retrospective de-identified VL data from 2013 to 2022 were evaluated to review program performance. Test volumes increased from 1,961,720 performed in 2013 to 45,334,864 in 2022. The median total in-laboratory turnaround time (TAT) ranged from 94 h (2015) to 51 h (2022). Implementation of two new assays improved median TATs in all laboratories. Samples of VL greater than 1000 copies/mL declined steadily. Despite initial increases, samples of fewer than 50 copies/mL stagnated at about 70% from 2019 and declined to 68% in 2022. Some variations between assays were observed. Overall, the SA VL program is successful. The scale of the VL program, the largest of its kind in the world by some margin, provides lessons for future public health programs dependent on laboratories for patient outcome and program performance monitoring.

HIV, logic and sex in Africa.

A widely accepted explanation of the dramatically high rates of HIV infection in sub-Saharan Africa appeals to a supposedly distinct model of sexual partnering, referred to as 'multiple concurrent partnerships' or 'concurrency.' We discuss two problems with the concurrency explanation, and argue that it does not contribute to understanding the unusual rates of HIV infection in the region. We argue that there is no single 'concurrency hypothesis,' and the term 'concurrency' is imprecise and does not pick out an explanatorily distinct form of sexual behavior.

A Retrospective Medical Record Review to Describe Health Status and Cardiovascular Disease Risk Factors of Bus Drivers in South Africa.

Cardiovascular disease (CVD) is the leading cause of death globally. The occupational challenges of bus drivers may increase their risk of CVD, including developing obesity, hypertension, and diabetes. We evaluated the medical records of 266 bus drivers visiting an occupational medical practice between 2007 and 2017 in Johannesburg, South Africa, to determine the health status of bus drivers and investigate risk factors for CVD, and their impact on the ability to work. The participants were in majority male (99.3%) with a median age of 41.2 years (IQR 35.2); 23.7% were smokers, and 27.1% consumed alcohol. The median body mass index (BMI) was 26.8 m/kg2 (IQR 7.1), with 63.1% of participants having above normal BMI. Smoking, BMI, and hypertension findings were in line with national South African data, but diabetes prevalence was far lower. Undiagnosed hypertension was found in 9.4% of participants, uncontrolled hypertension in 5.6%, and diabetes in 3.0%. Analysis by BMI category found that obesity was significantly associated with increased odds of hypertension. Uncontrolled hypertension was the main reason for being deemed 'unfit to work' (35.3%). Our research highlights the need for more regular screening for hypertension and interventions to address high BMI.

Coronavirus Host Genomics Study: South Africa (COVIGen-SA).

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA-a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Preparing for the next pandemic: Lessons from rapid scale-up of SARS-CoV-2 testing in a South African high-throughput automated HIV molecular laboratory.

Africa's readiness to respond to the SARS-COV-2 pandemic was tested due to reliance on rapid turn-around-time of polymerase chain reaction results for clinical management, isolation and quarantine decisions. The NHLS HIV Molecular Laboratory in Johannesburg, South Africa, is one of the largest automated HIV molecular laboratories worldwide. Despite its extensive molecular capacity and experience in managing high volumes acquired from a large HIV program, significant challenges were encountered during its rapid transition to large scale SARS-CoV-2 testing. We describe the strategies employed to manage these challenges that resulted in a 30% improvement in SARS-CoV-2 test turn-around-time during the first wave peak during which approximately 25000 samples were tested per month, and further improvement during the second wave peak, with 81% within targeted turn-around-time.

Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk.

Introduction: Insight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT). Methods: A cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel 'inflammation', allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors. Results: In total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 - 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only. Conclusion: HIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

What we have learned from antiretroviral treatment optimization efforts over the last 5 years?

Progression in the development of antiretroviral therapy has been remarkable, with new agents continuing to appear as options for modern regimens, including in low-and-middle income countries where the HIV epidemic is concentrated. Here, we reflect on progress made in guiding regimen changes to public health programmes, and the challenges facing selection of newer agents.

Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa.

OBJECTIVE: Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. DESIGN: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. METHODS: We compared changes in mean serum folate and occurrence of low serum folate (<14.0 nmol/l) at weeks 0, 12 and 24 across study arms. In ADVANCE, 1053 treatment-naïve participants were randomized to initiate tenofovir-alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG), tenofovir-disoproxil-fumarate (TDF)/FTC + DTG or TDF/FTC/efavirenz (EFV). RESULTS: Analysis includes 406 females, mean age 31.5 years and baseline CD4+ cell count 356 cells/µl. At baseline, folate concentrations were similar across treatment arms. However, serum folate increased over 12 weeks in the TAF/FTC + DTG arm (+4.0 ±â€Š8.1 nmol/l), while folate concentrations decreased slightly in the TDF/FTC + DTG arm (-1.8 ±â€Š8.9 nmol/l) and decreased in the TDF/FTC/EFV arm (-5.9 ±â€Š8.1 nmol/l). Women taking TDF/FTC/EFV had low folate concentrations at both 12 and 24 weeks compared with the other arms (P < 0.001). Of 26 women who became pregnant on study before week 24, folate concentrations increased between baseline and 12 weeks by a mean 2.4 ±â€Š7.1 nmol/l in the TAF/FTC + DTG arm and 2.3 ±â€Š8.4 nmol/l in the TDF/FTC + DTG arm, but decreased by -3.3 ±â€Š8.1 with TDF/FTC/EFV arm. CONCLUSION: Unexpectedly, no declines were noted in the dolutegravir-containing arms, and concentrations were considerably higher than in the EFV arm. The possibility that dolutegravir may block cellular uptake of folate warrants investigation.

Weight gain stopping/switch rules for antiretroviral clinical trials.

Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens' potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when "too much" weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.

Working nights and lower leisure-time physical activity associate with chronic pain in Southern African long-distance truck drivers: A cross-sectional study.

BACKGROUND: In South Africa, the trucking industry employs over 70,000 people and the prevalence of chronic pain in this occupational group was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so. METHODS: Southern African male, long-distance truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n = 614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated. RESULTS: Multivariate analysis showed that working ≥ 2 nights/week (OR = 2.68, 95% CI = 1.55-4.68) was associated with chronic pain and physical activity was protective (OR = 0.97, 95% CI 0.95-0.98). In an exploratory analysis, greater depressive symptoms (p = 0.004), daytime sleepiness (p = 0.01) and worse sleep quality (p = 0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p = 0.006), but not daytime sleepiness or depressive symptoms (p>0.05). CONCLUSIONS: There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

Differential Responsiveness of the Platelet Biomarkers, Systemic CD40 Ligand, CD62P, and Platelet-Derived Growth Factor-BB, to Virally-Suppressive Antiretroviral Therapy.

Systemic biomarkers of inflammation, including cytokines and chemokines, are potentially useful in the management of both HIV infection and non-AIDS-defining disorders. However, relatively little is known about the utility of measurement of circulating biomarkers of platelet activation as a strategy to monitor the efficacy of combination antiretroviral therapy (cART), as well as the persistence of systemic inflammation following virally-suppressive therapy in HIV-infected persons. These issues have been addressed in the current study to which a cohort consisting of 199 HIV-infected participants was recruited, 100 of whom were cART-naïve and the remainder cART-treated and virally-suppressed. Fifteen healthy control participants were included for comparison. The study focused on the effects of cART on the responsiveness of three biomarkers of platelet activation, specifically soluble CD40 ligand (sCD40L), sCD62P (P-selectin), and platelet-derived growth factor-BB (PDGF-BB), measured using multiplex suspension bead array technology. Most prominently sCD40L in particular, as well as sCD62P, were significantly elevated in the cART-naïve group relative to both the cART-treated and healthy control groups. However, levels of PDGF-BB were of comparable magnitude in both the cART-naïve and -treated groups, and significantly higher than those of the control group. Although remaining somewhat higher in the virally-suppressed group relative to healthy control participants, these findings identify sCD40L, in particular, as a potential biomarker of successful cART, while PDGF-BB may be indicative of persistent low-level antigenemia.